The purpose of this systematic review and meta-analysis of in vitro studies was to evaluate the effect of the 2780 nm Er,Cr:YSGG laser combined with casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) for enamel remineralisation. The electronic PubMed, Cochrane Library, Web of Science, and EMBASE databases were searched, with no language or date restrictions, up to January 2023. Two reviewers independently performed research information extraction and quality assessment. Continuous variables were analysed by standard mean difference (SMD) with a 95% confidence interval (CI). The statistical analyses were conducted using Review Manager (Version 5.4; Rev Man) and Cochrane Collaboration (2020). Finally, four trials were included for meta-analysis. According to the comprehensive results, the effect of the Er,Cr:YSGG laser combined with CPP-ACP on enamel remineralisation was significantly better than that of CPP-ACP alone: surface microhardness (SMD =  - 1.83, 95% CI: [- 2.98, - 0.69], P = 0.002); lesion depth (SMD = 6.63, 95% CI: [4.98, 8.28], P < 0.001). Under the limitations of this meta-analysis, the results show that the Er,Cr:YSGG laser combined with CPP-ACP has a better effect on enamel remineralisation than CPP-ACP alone. The combination of the Er,Cr:YSGG laser and CPP-ACP may be a feasible method to prevent and treat enamel demineralisation.© 2023. The Author(s).